Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells

C Gaggioli, S Hooper, C Hidalgo-Carcedo… - Nature cell …, 2007 - nature.com
C Gaggioli, S Hooper, C Hidalgo-Carcedo, R Grosse, JF Marshall, K Harrington, E Sahai
Nature cell biology, 2007nature.com
Imaging of collectively invading cocultures of carcinoma cells and stromal fibroblasts reveals
that the leading cell is always a fibroblast and that carcinoma cells move within tracks in the
extracellular matrix behind the fibroblast. The generation of these tracks by fibroblasts is
sufficient to enable the collective invasion of the squamous cell carcinoma (SCC) cells and
requires both protease-and force-mediated matrix remodelling. Force-mediated matrix
remodelling depends on integrins α3 and α5, and Rho-mediated regulation of myosin light …
Abstract
Imaging of collectively invading cocultures of carcinoma cells and stromal fibroblasts reveals that the leading cell is always a fibroblast and that carcinoma cells move within tracks in the extracellular matrix behind the fibroblast. The generation of these tracks by fibroblasts is sufficient to enable the collective invasion of the squamous cell carcinoma (SCC) cells and requires both protease- and force-mediated matrix remodelling. Force-mediated matrix remodelling depends on integrins α3 and α5, and Rho-mediated regulation of myosin light chain (MLC) activity in fibroblasts, but these factors are not required in carcinoma cells. Instead, carcinoma cells use Cdc42 and MRCK (myotonic dystrophy kinase-related CDC42-binding protein kinases) mediated regulation of MLC to follow the tracks generated by fibroblasts.
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